Fianlimab and Cemiplimab as Total Neoadjuvant Therapy (TNT) For Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Major Pathologic Response (MPR) Rate by RECIST v1.1
研究概览
简要总结
This is a phase II, open label clinical trial determining efficacy of Fianlimab in combination with Cemiplimab in subjects with Melanoma. These are subjects who will have surgery to remove their cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years at the time of signing informed consent form (ICF) and able to independently complete informed consent. A certified translator must be used in the completion of informed consent for non-English speaking individuals.
- •Patients must have surgically resectable, macroscopic Stage IIIB-D cutaneous melanoma or oligometastatic resectable stage IV (M1a, M1b, and M1c) melanoma per American Joint Committee on Cancer 8th Edition Staging Criteria. Patients are eligible at the time of the initial diagnosis or recurrence after previous surgery. Patients should have > 1 RECIST measurable lesion.
- •Participants must have Eastern Cooperative Group (ECOG) performance status score of 0, 1 or 2 at initial screening.
- •Life expectancy of at least 12 weeks.
- •Adequate bone marrow, liver, and renal function:
- •Hemoglobin >8.0 g/dL
- •Platelets >75/mm3
- •ANC >1.5/mm3
- •Creatinine Clearance > 30mL/min
- •AST and ALT less than 3 times the Upper Limit of Normal. participants with Gilbert's syndrome are excluded if total bilirubin > 3.0 × ULN; or direct bilirubin > 1.5 × ULN
- •Total Bilirubin < 3.
- •Albumin ≥ 3.0 g/dL
- •Absolute neutrophil count ≥ 1.5 × 109/L
- •Absolute lymphocyte count ≥ 0.5 × 109/L
- •Women of childbearing potential must have had a negative pregnancy test performed within 7 days prior to the start of treatment.
- •Females of childbearing potential and males must be willing and able to use a highly effective method of contraception to avoid pregnancy for the duration of the study and for at least 6 months after the last dose of study treatment. Acceptable means of contraception are listed in the fianlimab institutional brochure.
- •Male participants must be willing to abstain from donating sperm from the time of enrollment until 6 months after administration of study interventions.
排除标准
- •Participants with visceral, bone, or brain metastases.
- •Participants with a local recurrence in scar or surgical bed of the primary melanoma as the sole site of disease.
- •Participants with N1a or N2a only disease.
- •Participants with a diagnosis of acral, ocular or mucosal melanoma.
- •Participants with a history of a malignant disease that can interfere with interpretation of study results.
- •Participants with previous treatment with investigational or standard immunotherapy for melanoma or other malignancy.
- •Patients with a history of myocarditis.
- •Patients with a TnT or troponin I (TnI) > 2x institutional ULN at baseline. Patients with Troponin T (TnT) or troponin levels between > 1 to 2x ULN are permitted if repeat levels within 24 hours are ≤ 1x ULN. If TnT or TnI levels are > 1 to 2x ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment by the investigator based on the medical judgement in the patient's best interest.
- •Participants with known untreated or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Known hypersensitivity to the active substances or to any of the excipients.
- •Participants with a known history of chronic viral infections as indicated below.
- •Known HBV infection defined as hepatitis B surface antigen reactive. NOTE: Participants with HBV infection on stable anti-viral therapy for > 4 weeks prior to the planned first study intervention and viral load confirmed as undetectable during Screening may be eligible.
- •Known active HCV infection defined as detectable HCV RNA (qualitative) infection. NOTE: History of HCV is not exclusionary if participant has received curative treatment and viral load is confirmed as undetectable during Screening.
- •HIV infection with CD4 count <200/microliter as measured within screening time period. Patients with HIV infectious should be on combination antiretroviral medication.
- •History or current evidence of significant (CTCAE grade ≥2) local or systemic infection (eg, cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication.
- •Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents except for the following: . The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment.
- •Participants with a history of allogeneic tissue/solid organ transplant.
- •Live vaccine within 30 days of the planned administration of a study drug.
- •Positive pregnancy test during screening. Pregnant or lactating women are prohibited from enrolling in this study.
- •Participants must not have any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study treatment administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results.
研究组 & 干预措施
3 doses of neoadjuvant of Fianlimab in combination with Cemiplimab
3 doses of neoadjuvant 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks, followed by Surgery and then 13 doses of 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks
干预措施: Fianlimab (Drug)
8 doses of neoadjuvant Fianlimab in combination with Cemiplimab
8 doses of neoadjuvant 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks, followed by Surgery and then 8 doses of 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks
干预措施: Fianlimab (Drug)
8 doses of neoadjuvant Fianlimab in combination with Cemiplimab
8 doses of neoadjuvant 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks, followed by Surgery and then 8 doses of 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks
干预措施: Cemiplimab (Drug)
6 doses of neoadjuvant Fianlimab in combination with Cemiplimab
6 doses of neoadjuvant 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks, followed by Surgery and then 10 doses of 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks
干预措施: Fianlimab (Drug)
3 doses of neoadjuvant of Fianlimab in combination with Cemiplimab
3 doses of neoadjuvant 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks, followed by Surgery and then 13 doses of 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks
干预措施: Cemiplimab (Drug)
6 doses of neoadjuvant Fianlimab in combination with Cemiplimab
6 doses of neoadjuvant 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks, followed by Surgery and then 10 doses of 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks
干预措施: Cemiplimab (Drug)
结局指标
主要结局
Major Pathologic Response (MPR) Rate by RECIST v1.1
时间窗: 16 months
Evaluate the major pathologic response (MPR), defined as pathologic complete response (pCR) + pathologic near complete response (pnCR) after treatment with dual checkpoint blockade in the index lymph node of Cohort 2 and Cohort 3
次要结局
- Major Pathologic Response (MPR) Rate by RECIST v1.1(16 months)
- Objective Response Rate (ORR) by RECIST v1.1(16 months)
- Event-Free Survival (EFS)(28 months)
- Number of Patients with Adverse Events(28 months)
- Number of Patients with Immune Related Adverse Events(28 months)
- Number of Patients who Discontinued Treatment Due to Reported Adverse Events(28 months)
研究者
Warren Chow
HS Clinical Professor
University of California, Irvine